DE102006033218B4 - Modified artificial tissue, process for its preparation and its use - Google Patents

Abstract

Modified artificial tissue comprising a coated mesh body or a coated perforated film made of a tear-resistant polymer, wherein the polymer is coated with an absorbent coating in the form of polysaccharides, by means of which liquids can be absorbed and retained, characterized in that the polysaccharides have functional groups, by means of which a medical adhesive can be chemically covalently bonded, the absorbent coating has no aldehyde groups and adheres to the mesh body or the perforated film through covalent bonds or ionic and adhesive interactions, and the polymer is provided with X-ray detectable markings.

Description

The invention relates to a modified artificial tissue, a process for its preparation and its use according to the claims.

For decades, a variety of fabrics and gauzes for a variety of uses are known.

Thus, for example, artificial tissue in the form of implant material in medicine, for example. For the treatment of fractures (hernias), tendons and organs and used to stabilize sutures. In this case, the artificial tissue, in particular if they have a net-like structure, with surgical clips or so-called tissue nails (as shown in FIG DE 103 00 787 A1 known) or fixed by suturing. Also implantation techniques are known without fixation, in which case the net weight is crucial for the adhesion of the implant to the natural tissue (this DE 102 21 320 A1 ).

The font DE 101 21 623 A1 discloses an artificial tissue of glass fiber (implant material) for the surgical closure of hernias, the surface of which is coated with silicone, wherein one or more biologically active substances are ionogenically or covalently bound to the silicone surface.

As silicones, which adhere well to glass according to Eugene G. Rochow: Silicon and Silicones, Springer Verlag Berlin-Heidelberg 1987, are after DE 101 21 623 A1 condensation-curing silicones used. The coating of the fabric takes place by intimately bringing the fabric into contact with silicone, with the aim of ensuring that the silicone completely envelops each individual spun yarn. This can be achieved by using silicones with a lower viscosity of less than 10,000 mPa · s, or else by reacting higher viscous silicones with suitable solvents, e.g. As heptane, diluted, the fabric (using pressure) completely soaked with this solution and then completely evaporates the solvent. Subsequently, the curing of the silicone takes place. The thickness of the silicone layer on the glass fiber fabric can be chosen freely by repeated repetition of the process. However, care is taken to ensure that the meshes of the tissue are not closed by the silicone, so that living cells can grow through this artificial tissue. By suitable choice of silicone types with different Shore hardness obtained with silicone coated glass fiber fabric of different streaks and flexibility. To increase the biocompatibility, in particular the cytocompatibility, one or more biologically active substances are ionically and / or covalently bound to the surface of the silicone. As a biologically active substance disclosed DE 101 21 623 A1 doing collagen, since it promotes cell adherence and cell proliferation of fibroblasts, ionogenically bound to the surface.

The disadvantage of these artificial fiberglass fabrics, just as with other known hernia nets, is that these tissues / nets must be sutured or stapled in their use, for example in surgical applications or in bookbinding, to have no or only insufficient retention capacity for liquids, such as adhesives have.

From the Scriptures DE 103 05 811 A1 It is known that the rapid ingrowth of implant material into the natural tissue and the reduction of scar contraction is ensured by the release of steroids and a corticosteroid.

To avoid adhesions with the natural tissues are out DE 203 06 635 U1 Nets, which consist of a composite of non-resorbable with absorbable materials known.

Hydrogel-coated nets can also be used as medical implant material (for this purpose, inter alia DE 101 06 546 A1 ).

From the Scriptures DE 103 18 801 A1 is a self-adhesive mesh is known, the adhesive property is caused by a polymer containing aldehydgruppenhaltigem. The aldehyde groups of the implant material should react with nucleophilic groups (for example amino groups) of the natural tissue.

The disadvantage of this solution is that the reaction is reversible, releasing cytotoxic aldehyde groups by the reverse reaction. In addition, the reaction according to DE 103 18 801 A1 presupposes the free accessibility of nucleophilic groups on the natural tissue. However, since the surface of the natural tissue is coated with proteins, fats or blood, the adhesive power of this covalent, reversible compound (bonding) is greatly reduced / decreased.

From the Scriptures DE 198 45 923 A1 A method of producing a hardcover book is known in which book block spines are fed by means of a spool machine to a composite web made of a paper-coated gauze. According to this document, the composite material is aftertreated by a sanforization process and has a flat crimp with a longitudinal extensibility between 5% and 15%.

The end of the composite web is according to DE 198 45 923 A1 supplied to the book block transversely to the longitudinal extent of the book block back and glued to the book block back. After cutting off the composite material web, the crimp is formed by trimming and gluing the supernatants on the pre- and post-shred paper, which has an extensibility transverse to the book block spine. The book block spine can then be rounded, with the crust stretching without losing stability or even tearing.

The book block composite material / backing material is a cotton fabric web that is pre-treated by washout, desizing, bleaching and drying and then laminated with a paper web by means of an adhesive. In this way, the composite material for smoothing and solidification is calendered, whereby the still-wet composite material web is compressed in the longitudinal direction in a fine-step, whereby a fine creping fixed by drying or composite material web is obtained.

The disadvantage of this method is that the backing material for liquids, such as the adhesive, has only an insufficient holding potential, so that the liquid, such as the adhesive drips from the backing material.

The font DE 36 19 531 A1 discloses an anatomical, cosmetic gauze for the cosmetic treatment of unesthetic skin manifestations of the face and body of a pure, close-knit cotton fabric cut to anatomical shapes and impregnated with oily or greasy carrier cosmetic substances, said gauze being applied by surface adhesion and there for a long enough time. The carriers used are according to DE 36 19 531 A1 to lanolin or vaseline compounds.

The retention capacity of these thicker cotton fabrics, in interplay with the higher viscosity liquids in the form of the lanolin or vaseline compounds, is sufficient for the cosmetic treatment. For example, for surgical applications, however, this thick cotton fabric with sufficient fluid retention capacity for highly viscous substances is not suitable.

From the Scriptures DE 10 2004 046 019 A1 are known a method for coating a network, in particular for sports and recreation, and a network, in particular a volleyball net, football net, tennis net or ball net. It is known from this document that there is the difficulty that the material, in particular polyester or polyamide, from which the net threads are made, is not absorbent and has such a surface finish that the printing inks or spray paints commonly used for printing objects on it only very badly liable.

According to DE 10 2004 046 019 A1 a method for coating a network, in particular for sports and leisure, which comprises a network body with a plurality of meshes, which are bounded by net threads, and wherein the net threads in a region of the net body defining the optically visible character coating material, in particular Flock (plastic foam material), for example. By gluing, is applied.

From the Scriptures DE19746403A1 For example, there is known a resorbable polyester which is prepared in a crosslinking reaction with a peroxide which is simple and inexpensive to manufacture and has hydrolysis times, by virtue of which it can be used in particular in implant medicine, the resorbable polyester being insoluble in boiling chloroform Proportion of about 10 wt .-% or more, based on the total amount of the polyester having.

From the DE 103 18 801 A1 are implants with a flat carrier with two sides, wherein on at least one side of the carrier, a resorbable adhesive layer is provided, which is able to adhere to human and animal tissue known. The adhesive layer is self-adhesive and may be a polymer, such as a polysaccharide.

DE 101 06 546 A1 discloses a method for manufacturing a medical implant having a porous basic structure, e.g. B. polymer-based, and at least one polyethylene oxide and / or polyethylene glycol-containing hydrogel element, wherein an aqueous solution, aqueous liquid mixture or melt containing polyethylene oxide and / or polyethylene glycol, at least in some areas applied to the basic structure. Irradiation with gamma rays crosslinks to a hydrophilic hydrogel.

Out DE 2 220 871 B2 For example, there is known a method in the field of chamois leather, wherein a nonwoven substrate is exposed to a film-forming, vulcanizable coating composition, the solidification subsequently being solidified.

EP 1 216 717 A1 discloses reinforced, biocompatible tissue implants consisting of bioabsorbable foamed polymers having pores and a reinforcing component in the form of a braid, with both components of the implant hooking together. The foamed layer is multi-layered

WO 94/15651 A1 discloses powdery, crosslinked, aqueous liquids and blood-absorbing polymers (superabsorbents) formed from a) 55-99.9% by weight of polymerized, unsaturated, polymerizable, acid group-containing monomers which have been neutralized by at least 25 mol%, b) 0- 40 wt .-% of polymerized unsaturated monomers copolymerizable with a), c) 0.1-5.0 wt .-% of a crosslinking agent, d) 0-30 wt .-% of a water-soluble polymer, wherein 100 TL of particulate polymers with an aqueous solution of not more than 10 tsp of at least 10% phosphoric acid; and (a) 0,05-0,3 tsp of a compound capable of reacting with at least two carboxyl groups and containing no alkali salt-forming group in the molecule, and / or b) 0,05 -1 TL of a compound which can react with at least two carboxyl groups and contains an alkali salt-forming group in the molecule, mixed and heated to 150-250 ° C.

DE 195 40 656 C2 discloses an artificial tissue consisting of a moldable mixture of a hydrogel, an electrolyte, and combustible fibers, which mixture is useful for replicating organs, organ parts or organ systems.

The present invention seeks to remedy the shortcomings of the prior art in a simple manner in which a modified artificial fabric is provided which has a very small thickness (low weight per unit area), is flexible and at the same time has tensile strength, and is a good one Contains retention for a variety of liquids.

Moreover, it is the object of the present invention to provide a method for producing this modified artificial tissue, and to show various uses of the modified artificial tissue.

The above object is achieved by the features of the 1st, 4th and 8th claim and configured by the features of the subordinate claims advantageous.

The essence of the invention lies in the provision, production and use of modified artificial tissue comprising a coated network body or a coated perforated film, wherein the network body or the perforated film is coated with a surface-structure-forming substance in which this substance is a Absaugbeschichtung, particularly preferred is a fluffy surface structure.

By means of the absorbent coating according to the invention, a particularly effective absorption / retention of a great variety of liquids, in particular a medical adhesive, is effected. As a result, the sucked / retained liquids do not drip off the artificial tissue.

In the case of the medical adhesive, this leads to the fact that no dripping of the adhesive can occur on natural tissue not involved in the operation, which avoids damage.

According to the invention, the surface-structure-forming substance according to the invention has functional groups, by means of which the medical adhesive reacts chemically to form covalent bonds.

The invention will be explained in more detail below.

The modified artificial tissue according to the invention comprises a coated mesh body or a coated perforated foil, wherein the mesh body or the perforated foil is coated with a surface-structure-forming substance.

Formed by the surface structure forming substance is a wicking coating which is gel, foam or film like and has no aldehyde groups, which substance is a degradable polysaccharide.

Particularly advantageously, the absorbent coating is a fluffy Oberfächenstruktur consisting of polysaccharides, which may be natural or chemically modified, with mixtures of polysaccharides, which are given to each other and / or each other, are within the scope of the invention.

According to the invention, moreover, the surface-structure-forming substance adheres to the network body or the perforated film by covalent bonds or ionic and adhesive interactions.

The mesh body or the perforated film per se consist of a tear-resistant polymer, preferably of polytetrafluoroethylene, polyester polyamide, polypropylene or polyaramid.

• 1. Anordnen der Netzfäden auf einer Oberfläche,
• 2. Ausrichten der Netzfäden auf der Oberfläche in der Art und Weise, dass die von den Netzfäden einer Masche begrenzte Maschenfläche bezogen auf die Maschenfläche des Netzes im aufgespannten Zustand verkleinert ist,
• 3. Verbinden der Netzfäden und
• 4. Aufbringen des Oberflächenstruktur-bildenden Stoffes auf den Netzkörper.

The modified artificial fabric according to the present invention is produced by forming a mesh body comprising a plurality of meshes bounded by net threads, to which a surface-structure-forming matter is applied to the net threads. For this, the following process steps are carried out:

• 1. placing the net threads on a surface,
• 2. aligning the net threads on the surface in such a way that the mesh area bounded by the net threads of a mesh is reduced in the stretched-up state with respect to the mesh surface of the net,
• 3. Join the net threads and
• 4. application of the surface structure-forming substance on the network body.

The joining of the net threads in step 3 takes place by gluing, welding or linking.

Alternatively, the fabric of the invention may be made by weaving or knitting the net threads of the prior art and subsequently provided with the absorbent coating.

• 1. Anordnen der Folie in einer Ebene,
• 2. Durchlöchern der Folie,
• 3. Aufbringen des Oberflächenstruktur-bildender Stoffes auf die perforierte (durchlöcherte) Folie.

A further possibility for producing the modified artificial tissue according to the invention is that the network body is produced from a film which comprises a multiplicity of holes which regularly or irregularly pass through them, by applying to the film a surface structure-forming substance , For this, the following process steps are carried out:

• 1. Arrange the slide in a plane
• 2. perforate the film,
• 3. Apply the surface texture forming agent to the perforated (perforated) film.

The perforation of the film in step 2 is carried out by piercing, laser scanning, piercing or through etching.

As an alternative to perforating, it is also possible to provide the film base material with additives which are dissolved out of the film base body after the finished product has been produced. Aggregates can be, for example, salts.

Alternatively, the film of the invention may be made according to the prior art and subsequently provided with the absorbent coating.

• – zum Verkleben von biologischem, tierischem oder menschlichem Gewebe,
• – zum Verkleben eines Buchblockes eines Buches

oder bspw. als Trägermaterial für kosmetische Stoffe und Flüssigkeiten.The fabric according to the invention has the advantage that it has a very small thickness, is flexible and at the same time resistant to tensile stress, and has good retention properties for a wide variety of liquids due to the modified (fluffy) surface, so that it can be used in a very wide variety of applications, such as, for example behind adhesive material:

• For bonding biological, animal or human tissue,
• - for gluing a book block of a book

or, for example, as a carrier material for cosmetic substances and liquids.

About the properties of the formed by means of the surface structure-forming substance absorbent coating, such as, for example, the thickness, porosity, hydrophilicity or lipophilicity, the absorbency of the artificial tissue according to the invention is adjustable.

Adhesives based on isocyanates or cyanoacrylates may preferably be used as medical adhesives for bonding the implant nets / sheets according to the invention.

For better handleability, the fabric according to the invention can be provided on one or both sides with a protective film, wherein the surface structure-forming substance can be on one side or on both sides on the net / the perforated film.

According to the invention, the fabric according to the invention can also be provided with X-ray-detectable markings and / or have for the specific uses a defined predetermined geometric shape and / or special reinforcement points / surfaces for bonding / sewing.

An advantage of the modified artificial tissue according to the invention is that absorption of liquids, for example medical glue, takes place both through the coating of surface-structure-forming substance and through the mesh interstices of the net or the recesses of the porous foil. In this case, the modified artificial tissue can be soaked shortly before its use with the liquid, for example an adhesive, or already well before its use, the liquid, for example. An adhesive wear.

1st embodiment

A polyester mesh is dipped in an alcoholic solution containing a heterobifunctional coupling reagent containing a photoactivatable azide group and an amino group and then dried. Exposure to UV light causes the coupling reagent to react with the polyester network. The network surface thus provided with amino groups is then reacted with oxidized starch to form imino groups. The build-up of the coating is continued by alternately dipping the mesh in a diamine solution and in an oxidized starch solution. Subsequently, the imino groups and excess aldehyde groups of the oxidized starch in the coating are reduced by means of a solution of sodium borohydride, so that a reverse reaction is prevented. At the end of this reaction step, neither aldehyde nor imino groups are present. Before bonding, the coated network is impregnated with cyanomethyl acrylate.

2nd embodiment

A network of polyamide is immersed in an alcoholic solution of heterobifunctional coupling reagent containing a photoactivatable azide group and an aldehyde group, and then dried. Exposure to UV light causes the coupling reagent to react with the network. The network surface thus provided with aldehyde groups is then reacted with deacetylated chitosan to form imino groups. The buildup of the coating is continued by alternately dipping the mesh in an aqueous glutaraldehyde solution and in a deacetylated chitosan solution.

This is followed by a reaction of the excess aldehyde groups with amino-styrene. (The styrene unit coupled to the coating by this reaction step provides the unsaturated carbon double bonds for anionic polymerization with the cyanomethyl acrylate.) After reaction with an aqueous solution of sodium borohydride to chemically reduce excess aldehyde and / or imino groups, the implant is rinsed and dried. Before bonding, the coated network is impregnated with cyanomethyl acrylate.

3rd embodiment

A polypropylene mesh is dipped in an alcoholic solution of heterobifunctional coupling reagent containing a photoactivatable azide group and an amino group and then dried. Exposure to UV light causes the coupling reagent to react with the polyester network. The network surface thus provided with amino groups is then reacted with oxidized starch to form imino groups. The build up of the coating is continued by alternately dipping the mesh in a diamine solution and an oxidized starch solution. Subsequently, the imino groups and excess aldehyde groups of the oxidized starch in the coating are reduced by means of a solution of sodium borohydride. The coated net is freeze-dried. Before bonding, the coated network is impregnated with hexamethylene diisocyanate.

4th embodiment

A network of polymer propylene is reacted by radical graft polymerization with methacrylic acid involving Fenton's Reaganz. The carboxyl groups formed on the surface are activated with a water-soluble carbodiimide and reacted with chitosan solution. The modified net is placed in a freshly prepared solution of chitosan and oxidised dextran. By adding an amine with double bond (para-aminostyrene), the free aldehyde groups of the oxidized dextran component are saturated. Subsequently, a reduction with sodium borohydride. After freeze-drying, a net is obtained which is covalently coated and surrounded by the polysaccharide. Before bonding, the isocyanate adhesive is dropped onto the net. The polysaccharide fabric absorbs the adhesive and additionally forms a covalent bond with the double bonds present.

In the laboratory test, peritoneum, muscle tissue, liver tears as an example of organ tissue, tendons and blood vessels could be pasted in the laboratory test using the flat implants produced using the exemplary embodiments 1-4.

All features described in the description, the exemplary embodiments and the following claims may be essential to the invention both individually and in any combination with one another.

Claims (11)

A modified artificial fabric comprising a coated mesh body or a coated perforated sheet of a tear-resistant polymer, the polymer being coated with a polysaccharide absorbent coating by which liquids are absorbable and retainable, characterized in that the polysaccharides have functional groups by means of which a medical adhesive is chemically covalently attachable, the wicking coating has no aldehyde groups and is attached by covalent bonds or ionic and adhesive interactions to the mesh body or the perforated film and the polymer is provided with X-ray detectable markers. A modified artificial fabric according to claim 1, characterized in that the polymer is polytetrafluoroethylene, polyester, polyamide, polypropylene or polyaramid. Modified artificial tissue according to claim 1, characterized in that the mesh body or the perforated foil carries a foil. A method of making a modified artificial fabric according to claim 1, wherein the mesh body comprises a plurality of meshes bounded by net threads, and wherein a surface structure forming substance is applied to the net threads, comprising the following steps: a) arranging the net threads on a surface, b) aligning the net threads on the surface in such a way that the mesh surface bounded by the net threads of a mesh is reduced in the stretched state relative to the mesh surface of the mesh, c) joining the net threads and d) applying the surface structure -forming substance on the network body. A method for producing a modified artificial tissue according to claim 4, characterized in that the bonding is carried out by gluing, welding or linking. A method for producing a modified artificial fabric according to claim 1, wherein the network body comprises a plurality of stitches bounded by net threads and wherein a surface structure forming substance is applied to the net threads, comprising the following method steps: a) weaving or knitting the net threads and b) applying the surface structure-forming substance to the network body. A process for producing a modified artificial fabric according to claim 1, wherein the film comprises a plurality of holes which regularly or irregularly pass completely through which a surface structure-forming substance is applied to the film, comprising the following process steps: a) arranging the film in a plane, b) perforating the film, c) applying the surface structure-forming substance to the perforated (perforated) film. Use of the modified artificial tissue according to one or more of claims 1 to 4 as a back-adhesive material. Use according to claim 8 in medicine for bonding biological, animal or human tissue. Use according to claim 8 in the book production for gluing a book block of a book. Use of the modified artificial tissue according to one or more of claims 1 to 4 as a carrier material.